A Medical Molecular Mechanism

Tired of hearing about halogenation and hydrogenation reaction mechanisms? Keep that organic chemistry book open, because it gets better:

At Columbia University Medical Center, researchers have discovered the reason for the build-up of harmful proteins in Parkinson’s patients. The scientists have worked out a mechanism for the build-up of a class of proteins known as polyamines, a known neuron-killer involved in Parkinson’s disease. High-resolution fMRI scans showed a brainstem region in Parkinson’s patients that produced less activity than the same region in healthy patients. Based on tissue samples from deceased patients, Dr. Scott A. Small of Columbia posits that SAT1, an enzyme that breaks down polyamines, might play a role in the development of Parkinson’s and thus explain the differences in the fMRI studies.

Experiments in yeast, mice and humans have shown the pathogenicity of polyamines. At Brandeis University, researchers showed that yeast cells engineered to produce polyamines died more quickly than yeasts that were not. Scientists at UC San Diego School of Medicine used mice to both demonstrate the connection between SAT1, polyamines and Parkinson’s and to show that SAT1-targeting drugs could help to deter the progression of the disease. In addition, Columbia researchers have studied the SAT1 gene and found a genetic variation that is present in Parkinson’s patients but absent in healthy control subjects.

Several years ago, polyamine-lowering drugs were being studied as potential cancer treatments. It was unclear in these trials whether or not the drugs could penetrate the blood-brain barrier. The ability to penetrate the blood-brain barrier is crucial for Parkinson’s treatments: if the drug cannot get through, it must be administered into the brain directly. Dr. Small’s lab is currently working on drugs that can pass through the blood-brain barrier so that Parkinson’s can be effectively treated with pills rather than brain surgery!